Sleep-Stage Correlates of Hippocampal Electroencephalogram in Primates

It has been demonstrated in the rodent hippocampus that rhythmic slow activity (theta) predominantly occurs during rapid eye movement (REM) sleep, while sharp waves and associated ripples occur mainly during non-REM sleep. However, evidence is lacking for correlates of sleep stages with electroencephalogram (EEG) in the hippocampus of monkeys. In the present study, we recorded hippocampal EEG from the dentate gyrus in monkeys overnight under conditions of polysomnographical monitoring. As result, the hippocampal EEG changed in a manner similar to that of the surface EEG: during wakefulness, the hippocampal EEG showed fast, desynchronized waves, which were partly replaced with slower waves of intermediate amplitudes during the shallow stages of non-REM sleep. During the deep stages of non-REM sleep, continuous, slower oscillations (0.5–8 Hz) with high amplitudes were predominant. During REM sleep, the hippocampal EEG again showed fast, desynchronized waves similar to those found during wakefulness. These results indicate that in the monkey, hippocampal rhythmic slow activity rarely occurs during REM sleep, which is in clear contrast to that of rodents. In addition, the increase in the slower oscillations of hippocampal EEG during non-REM sleep, which resembled that of the surface EEG, may at least partly reflect cortical inputs to the dentate gyrus during this behavioral state.     

Sleep and cortical temperature in the Djungarian hamster under baseline conditions and after sleep deprivation

The Djungarian hamster (Phodopus sungorus) is a markedly photoperiodic rodent which exhibits daily torpor under short photoperiod. Normative data were obtained on vigilance states, electroencephalogram (EEG) power spectra (0.25–25.0 Hz), and cortical temperature (T_CRT) under a 168 h light-dark schedule, in 7 Djungarian hamsters for 2 baseline days, 4 h sleep deprivation (SD) and 20 h recovery.During the baseline days total sleep time amounted to 59% of recording time, 67% in the light period and 43% in the dark period. The 4 h SD induced a small increase in the amount of non-rapid eye movement (NREM) sleep and a marked increase in EEG slow-wave activity (SWA; mean power density 0.75–4.0 Hz) within NREM sleep in the first hours of recovery. T_CRT was lower in the light period than in the dark period. It decreased at transitions from either waking or rapid eye movement (REM) sleep to NREM sleep, and increased at the transition from NREM sleep to waking or REM sleep. After SD, T_CRT was lower in all vigilance states.In conclusion, the sleep-wake pattern, EEG spectrum, and time course of T_CRT in the Djungarian hamster are similar to other nocturnal rodents. Also in the Djungarian hamster the time course of SWA seems to reflect a homeostatically regulated process as was formulated in the two-process model of sleep regulation.Abbreviations EEG electroencephalogram - EMG electromyogram - N NREM sleep - NREM non-rapid eye movement - R REM sleep - REM rapid eye movement - SD sleep deprivation - SWA slow-wave activity - T_CRT cortical temperature - TST total sleep time - VS vigilance state - W waking     

Sleep and EEG spectra in the pigeon (Columba livia) under baseline conditions and after sleep deprivation

Summary Sleep in adult domestic pigeons was studied by continuous 24-h recording of the EEG, EMG and EOG. Vigilance states were scored on the basis of behavioral observations, visual scoring of the polygraph records, and EEG power spectra.The animals showed a clear nocturnal preference for sleep. Throughout the dark period, EEG slow-wave activity was at a uniform level, whereas REM sleep (REMS) showed an increasing trend.EEG power density values differed significantly between the vigilance states. In general the values were highest in nonREM sleep (NREMS), intermediate in waking (W) and lowest in REMS.Twenty-four hour sleep deprivation reduced W and increased REMS, effects that are well documented in mammals. Unlike in mammals, EEG slow-wave activity remained unchanged, whereas EOG activity in W and NREMS was enhanced.Abbreviations EEG electroencephalogram - EMG electromyogram - EOG electrooculogram - SD sleep deprivation - L light - D dark - LD light dark - NREMS non rapid eye movement sleep - REMS REM sleep     

Effect of the GABAA agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects

Aging is associated with a dramatic decrease in sleep intensity and continuity. The selective GABA(A) receptor agonist gaboxadol has been shown to increase non-REM sleep and the duration of the non-REM episodes in rats and sleep efficiency in young subjects and to enhance low-frequency activity in the electroencephalogram (EEG) within non-REM sleep in both rats and humans. In this double-blind, placebo-controlled study, we investigated the influence of an oral dose of 15 mg of gaboxadol on nocturnal sleep and hormone secretion (ACTH, cortisol, prolactin, growth hormone) in 10 healthy elderly subjects (6 women). Compared with placebo, gaboxadol did not affect endocrine activity but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness and powerfully augmented low-frequency activity in the EEG within non-REM sleep. These findings indicate that gaboxadol is able to increase sleep consolidation and non-REM sleep intensity, without disrupting REM sleep, in elderly individuals and that these effects are not mediated by a modulation of hormone secretion.     

Inter-Hemispheric Oscillations in Human Sleep

Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG) patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability. We then implemented a new probability dependent, automatic classification of sleep states that agreed closely with conventional manual scoring during consolidated sleep. Furthermore, this analysis revealed a previously unrecognized, interhemispheric oscillation during rapid eye movement (REM) sleep. This quantitative approach provides a new way of examining the dynamic aspects of sleep, shedding new light on the physiology of human sleep.     

Ghrelin promotes slow-wave sleep in humans

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

No short-term effects of digital mobile radio telephone on the awake human electroencephalogram

A recent study reported the results of an exploratory study of alterations of the quantitative sleep profile due to the effects of a digital mobile radio telephone. Rapid eye movement (REM) was suppressed, and the spectral power density in the 8–13 Hz frequency range during REM sleep was altered. The aim of the present study was to illuminate the influence of digital mobile radio telephone on the awake electroencephalogram (EEG) of healthy subjects. For this purpose, we investigated 34 male subjects in a single-blind cross-over design experiment by measuring spontaneous EEGs under closed-eyes condition from scalp positions C₃ and C₄ and comparing the effects of an active (0.05 mW/cm²) and an inactive digital mobile radio telephone (GSM) system. During exposure of nearly 3.5 min to the 900 MHz electromagnetic field pulsed at a frequency of 217 Hz and with a pulse width of 580 μs, we could not detect any difference in the awake EEGs in terms of spectral power density measures. Bioelectromagnetics 18:172–176, 1997. © 1997 Wiley-Liss, Inc.     

The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice

A quantitative analysis of spindles and spindle-related EEG activity was performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep regulatory mechanisms was tested by investigating their occurrence during 24 h and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct spindle events were characterized as EEG oscillations with a dominant frequency approximately at 11 Hz. Spindles were most prominent during NREM sleep and increased before NREM-REM sleep transitions. Whereas spindles increased concomitantly with slow wave activity (SWA, EEG power between 0.5 and 4.0 Hz) at the beginning of the NREM sleep episode, these measures showed an opposite evolution prior to the transition to REM sleep. The 24-h time course of spindles showed a maximum at the end of the 12-h light period, and was a mirror image of SWA in NREM sleep. After 6 h SD the spindles in NREM sleep were initially suppressed, and showed a delayed rebound. In contrast, spindles occurring immediately before the transition to REM sleep were enhanced during the first 2 h of recovery. The data suggest that spindles in NREM sleep may be involved in sleep maintenance, while spindles heralding the transition to REM sleep may be related to mechanisms of REM sleep initiation.     

Development of the nocturnal sleep electroencephalogram in human infants

The development of nocturnal sleep and the sleep electroencephalogram (EEG) was investigated in a longitudinal study during infancy. All-night polysomnographic recordings were obtained at home at 2 wk and at 2, 4, 6, and 9 mo after birth (analysis of 7 infants). Total sleep time and the percentage of quiet sleep or non-rapid eye movement sleep (QS/NREMS) increased with age, whereas the percentage of active sleep or rapid eye movement sleep (AS/REMS) decreased. Spectral power of the sleep EEG was higher in QS/NREMS than in AS/REMS over a large part of the 0.75- to 25-Hz frequency range. In both QS/NREMS and AS/REMS, EEG power increased with age in the frequency range <10 Hz and >17 Hz. The largest rise occurred between 2 and 6 mo. A salient feature of the QS/NREMS spectrum was the emergence of a peak in the sigma band (12-14 Hz) at 2 mo that corresponded to the appearance of sleep spindles. Between 2 and 9 mo, low-frequency delta activity (0.75-1.75 Hz) showed an alternating pattern with a high level occurring in every other QS/NREMS episode. At 6 mo, sigma activity showed a similar pattern. In contrast, theta activity (6.5-9 Hz) exhibited a monotonic decline over consecutive QS/NREMS episodes, a trend that at 9 mo could be closely approximated by an exponential function. The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleep homeostasis goes through a period of maturation. Theta activity and not delta activity seems to reflect the dissipation of sleep propensity during infancy.     

Muscle tone regulation during REM sleep: neural circuitry and clinical significance

Rapid eye movement (REM) sleep is a distinct behavioral state characterized by an activated cortical and hippocampal electroencephalogram (EEG) and concurrent muscle atonia. Research conducted over the past 50 years has revealed the neuronal circuits responsible for the generation and maintenance of REM sleep, as well as the pathways involved in generating the cardinal signs of REM sleep such as cortical activation and muscle atonia. The generation and maintenance of REM sleep appear to involve a widespread network in the pons and medulla. The caudal laterodorsal tegmental nucleus (cLDT) and sublaterodorsal nucleus (SLD) within the dorsolateral pons contain REM-on neurons, and the ventrolateral periaqueductal grey (vlPAG) contains REM-off neurons. The interaction between these structures is proposed to regulate REM sleep amounts. The cLDT-SLD neurons project to the basal forebrain via the parabrachial-precoeruleus (PB-PC) complex, and this pathway may be critical for the EEG activation seen during REM sleep. Descending SLD glutamatergic projections activate the ventromedial medulla, and spinal cord interneurons mediate muscle atonia and suppress phasic muscle twitches in spinal musculature. In contrast, phasic muscle twitches in the masseter muscles may be driven by glutamatergic neurons in the rostral parvicellular reticular nucleus (PCRt); however, the brain region responsible for generating phasic twitches in the other cranial muscles including facial muscles and tongue are not clear.     

Evaluation of two minimally invasive techniques for electroencephalogram recording in wild or freely behaving animals

Insight into the function of sleep may be gained by studying animals in the ecological context in which sleep evolved. Until recently, technological constraints prevented electroencephalogram (EEG) studies of animals sleeping in the wild. However, the recent development of a small recorder (Neurologger 2) that animals can carry on their head permitted the first recordings of sleep in nature. To facilitate sleep studies in the field and to improve the welfare of experimental animals, herein, we test the feasibility of using minimally invasive surface and subcutaneous electrodes to record the EEG in barn owls. The EEG and behaviour of four adult owls in captivity and of four chicks in a nest box in the field were recorded. We scored a 24-h period for each adult bird for wakefulness, slow-wave sleep (SWS), and rapid-eye movement (REM) sleep using 4 s epochs. Although the quality and stability of the EEG signals recorded via subcutaneous electrodes were higher when compared to surface electrodes, the owls’ state was readily identifiable using either electrode type. On average, the four adult owls spent 13.28 h awake, 9.64 h in SWS, and 1.05 h in REM sleep. We demonstrate that minimally invasive methods can be used to measure EEG-defined wakefulness, SWS, and REM sleep in owls and probably other animals.     

Reduction of rapid eye movement (REM) sleep by glucose alone or glucose and insulin in rats

Administration of a high dose of glucose (2.5 g/kg, i.p.) that is known to produce severe hyperglycemia in euglycemic rats suppressed rapid eye movement (REM) sleep time significantly during the first three hours of 8 hr total electroencephalogram (EEG) recording period. Co-administration of glucose (2.5 g/kg, i.p.) and a non-convulsive dose of insulin (1.0 I.U./kg, i.p.) produced a significant reduction in REM sleep time during 1st through 5th hour and an increase in slow-wave sleep (NREM) time in the 3rd and 4th hour of 8 hr total EEG recording period. However, awake, NREM and REM sleep time in the 8 hr total EEG recording period were unaffected by either glucose alone or glucose plus insulin treatments. These results strongly suggest that the insulin's effects on the sleep-awake cycle i.e. reduction in REM and a slight increase in NREM sleep times of rats is not due to indirect effects of insulin on the central nervous system via hypoglycemia as reported by us previously, but could possibly be due to its direct effects on brain chemistry of neurotransmitters such as serotonin, catecholamines and acetylcholine which are believed to modulate the sleep-awake cycle pattern in rats.     

Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from "without HE" or "minimal HE" to "overt HE", correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p?=?0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.     

Individual differences in the effects of mobile phone exposure on human sleep: rethinking the problem

Mobile phone exposure‐related effects on the human electroencephalogram (EEG) have been shown during both waking and sleep states, albeit with slight differences in the frequency affected. This discrepancy, combined with studies that failed to find effects, has led many to conclude that no consistent effects exist. We hypothesised that these differences might partly be due to individual variability in response, and that mobile phone emissions may in fact have large but differential effects on human brain activity. Twenty volunteers from our previous study underwent an adaptation night followed by two experimental nights in which they were randomly exposed to two conditions (Active and Sham), followed by a full‐night sleep episode. The EEG spectral power was increased in the sleep spindle frequency range in the first 30 min of non‐rapid eye movement (non‐REM) sleep following Active exposure. This increase was more prominent in the participants that showed an increase in the original study. These results confirm previous findings of mobile phone‐like emissions affecting the EEG during non‐REM sleep. Importantly, this low‐level effect was also shown to be sensitive to individual variability. Furthermore, this indicates that previous negative results are not strong evidence for a lack of an effect and, given the far‐reaching implications of mobile phone research, we may need to rethink the interpretation of results and the manner in which research is conducted in this field. Bioelectromagnetics 33:86–93, 2012. © 2011 Wiley Periodicals, Inc.     

Gamma band EEG activity is enhanced after the occurrence of rapid eye movement during human REM sleep

Sleep and Biological Rhythms - This study investigated changes in gamma band (35–44 Hz) EEG activity associated with rapid eye movement (REM) during human REM sleep. Polysomnograms of eight...     

Sequential analysis of the brain's transfer properties during consecutive REM episodes

Classical analysis of the spontaneous sleep EEG has revealed alterations of REM sleep in psychiatric diseases and under the influence of drugs. In order to elucidate possible functional differences between different REM episodes even in healthy subjects we investigated in 10 volunteers the transfer properties of the brain by measuring auditory (AEP) and visual evoked potentials (VEP) from scalp positions F_z, C_z and P_z during the night. According to linear system theory we computed the so-called amplitude-frequency characteristics (AFC) from averaged AEPs and VEPs during the first and each of the following 3 REM episodes. These functions describe the relationship between the input and output of the investigated system. A 3-factorial analysis of variances with the independent factors frequency band, REM episode and electrode position revealed a statistically significant main effect for the factor REM episode under auditory stimulation (P = 0.05), whereas no significant main effect for REM episode was found under visual stimulation (P = 0.88). Applying a 2-factorial analysis of variance with the independent factors REM episode and electrode position in the case of auditory stimulation we could demonstrate a statistically significant main effect (P = 0.029) for the factor REM episode in the beta range (12.5–20 Hz). A subsequent analysis of contrasts revealed that the first REM episodes could be differentiated from each other. For auditory stimulation the beta resonance during the first REM episode appears enhanced compared to each of the later REM episodes. These findings point to a functional difference of the brain's transfer functions between the first and the 3 following REM episodes, indicating different information processing during consecutive paradoxical sleep.     

A probabilistic framework for a physiological representation of dynamically evolving sleep state

This work presents a probabilistic method for mapping human sleep electroencephalogram (EEG) signals onto a state space based on a biologically plausible mathematical model of the cortex. From a noninvasive EEG signal, this method produces physiologically meaningful pathways of the cortical state over a night of sleep. We propose ways in which these pathways offer insights into sleep-related conditions, functions, and complex pathologies. To address explicitly the noisiness of the EEG signal and the stochastic nature of the mathematical model, we use a probabilistic Bayesian framework to map each EEG epoch to a distribution of likelihoods over all model sleep states. We show that the mapping produced from human data robustly separates rapid eye movement sleep (REM) from slow wave sleep (SWS). A Hidden Markov Model (HMM) is incorporated to improve the path results using the prior knowledge that cortical physiology has temporal continuity.